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APhA Staff

Can lowering BP prevent diabetes?

Lowering BP is an established strategy for preventing vascular complications of diabetes, but can it prevent diabetes?

An international group of researchers led by Kazem Rahimi, FCRP, of the University of Oxford (UK) investigated this question using individual participant data from major randomized controlled trials. The study, published in the November 13, 2021, issue of The Lancet, investigated the differential effects of 5 major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes.

An individual participant data network meta-analysis using data from 22 studies conducted between 1973 and 2008 that was obtained by the Blood Pressure Lowering Treatment Trialists’ Collaboration at Oxford University was used in the study. All primary and secondary prevention trials that used a specific class (or classes) of antihypertensive drugs versus placebo or other classes of BP-lowering medications and had at least 1,000 person-years were included. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded.

Of the over 145,000 participants in the one-stage individual participant data meta-analysis, fewer than 10,000 participants were diagnosed with new-onset type 2 diabetes.

The analysis showed that reduction of systolic BP by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11%. In comparison to placebo, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers reduced the risk of new-onset type 2 diabetes; however, the use of β blockers and thiazide diuretics increased this risk, and no material effect was found for calcium channel blockers.

The authors concluded that reduction of BP is an effective strategy for the prevention of new-onset type 2 diabetes, but that different medications vary in their ability to reduce diabetes onset, with angio-
tensin-converting enzyme inhibitors and angiotensinII receptor blockers having the most favorable outcomes.

Opioids after orthopedic surgery may not be necessary

Patients with a surgically managed fracture are commonly discharged from the hospital with a strong opioid prescription, but would mild opioid treatment be just as effective?

Researchers at the University of New South Wales (Australia) conducted a randomized clinical trial of 120 patients after surgical fixation of acute orthopedic fractures and found that oxycodone did not provide better pain relief than combination acetaminophen and codeine during the first 7 days after surgery. The study was published online on November 17, 2021, in JAMA Network Open.

Patients were given either oxycodone HCL (5 mg or 10 mg) or combination acetaminophen/codeine (500 mg/8 mg or 1,000 mg/16 mg) 4 times daily for a maximum of 3 weeks. The primary outcome was the mean  daily pain scores, on a scale of 1 to 10, that were collected during the first week of treatment. The mean daily pain score was 4.04 in the oxycodone group and 4.54 in the acetaminophen/codeine group. The researchers note that the between-group difference was not statistically significant and that strong opioid use after orthopedic surgery may not be needed.

Treating hypertension in patients with advanced CKD with thiazide diuretics

Hypertension is often poorly controlled in patients with advanced CKD, making thiazide or thiazide-like diuretics important agents for lowering BP in these patients. In a study published on November 5, 2021, in the New England Journal of Medicine, researchers at the Indiana University School of Medicine and the Richard L. Roudebush Veterans Affairs Medical Center (Indianapolis), investigated the efficacy of chlorthalidone, a thiazide-like diuretic, among patients with advanced CKD.

More than 160 patients with stage 4 CKD and poorly controlled hypertension, as confirmed by 24-hour ambulatory BP monitoring, were assigned to groups to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo. The primary outcome was the change in 24-hour ambulatory systolic BP from baseline to 12 weeks. Secondary outcomes were the change in urinary albumin-to-creatinine ratio, N-terminal pro–B-type natriuretic peptide level, plasma renin and aldosterone levels, and total body volume from baseline to 12 weeks. Safety was also assessed.

At study initiation, the mean 24-hour ambulatory systolic BP among participants was 142.6 mm Hg in the chlorthalidone group and 140.1 mm Hg in the placebo group. The adjusted change in 24-hour systolic BP from baseline to 12 weeks was −11.0 mm Hg in the chlorthalidone group and −0.5 mm Hg in the placebo group. The percent change in the urinary albumin-to-creatinine ratio from baseline to 12 weeks was lower in the chlorthalidone group than in the placebo group by 50 percentage points. However, hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia occurred more frequently in the chlorthalidone group than in the placebo group.

The authors note that chlorthalidone should be used with caution in patients receiving loop diuretics due to the risk of an increase in the serum creatinine level and because the lowest dose of chlorthalidone produced most of the BP-lowering effect it may be the safest dose to use. A reduction in the dose of the loop diuretic may also be needed. In addition, the researchers note that the trial had several limitations, including the relatively small size and the underrepresentation of women (22% of participants).

Study sheds light on antibiotic treatment dose for children with CAP

Because the optimal dose and duration of oral amoxicillin are unclear for children with

Because the optimal dose and duration of oral amoxicillin are unclear for children with community-acquired pneumonia (CAP) who are discharged from an emergency department, observational unit, or inpatient ward, the CAP-IT Trial Group, led by Julia Bielicki, PhD, of the University College London investigated whether lower-dose amoxicillin is as effective as a higher dose as well as  how a 3-day treatment compares to a 7-day treatment.

The study, published in the November 2, 2021, issue of JAMA, involved a multicenter, randomized, 2 × 2 factorial noninferiority trial enrolling 824 children (aged 6 months and older) with clinically diagnosed CAP treated with amoxicillin on discharge from emergency departments and inpatient wards of 29 hospitals between February 2017 and April 2019.

Children received oral amoxicillin at a lower dose (35–50 mg/kg/d) or higher dose (70–90 mg/kg/d), for either 3 or 7 days. The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization.

Results of the investigation showed that of the more than 800 participants randomized into 1 of the 4 groups, antibiotic retreatment was indicated in 12.6% of patients receiving the lower dose compared with 12.4% of patients receiving the higher dose. Retreatment was indicated in 12.5% of patients receiving the 3-day treatment compared with 12.5% receiving the 7-day treatment. Both groups demonstrated noninferiority, with no significant interaction between dose and duration.

The authors noted that although lower-dose outpatient oral amoxicillin was noninferior to a higher dose, and 3-day duration was noninferior to 7-day treatment, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideraation when interpreting the findings.